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Quantitative Fluxomics of Circulating Metabolites

机译：循环代谢物的定量血型组

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摘要

Mammalian organs are nourished by nutrients carried by the blood circulation. These nutrients originate from diet and internal stores, and can undergo various interconversions before their eventual use as tissue fuel. Here we develop isotope tracing, mass spectrometry, and mathematical analysis methods to determine the direct sources of circulating nutrients, their interconversion rates, and eventual tissue-specific contributions to TCA cycle metabolism. Experiments with fifteen nutrient tracers enabled extensive accounting for both circulatory metabolic cycles and tissue TCA inputs, across fed and fasted mice on either high-carbohydrate or ketogenic diet. We find that a majority of circulating carbon flux is carried by two major cycles: glucose-lactate and triglyceride-glycerol-fatty acid. Futile cycling through these pathways is prominent when dietary content of the associated nutrients is low, rendering internal metabolic activity robust to food choice. The presented in vivo flux quantification methods are broadly applicable to different physiological and disease states.
机译：哺乳动物的器官由血液循环所携带的营养物质提供营养。这些营养素来源于饮食和内部储存，在最终用作组织燃料之前，可以进行各种相互转化。在这里，我们开发了同位素示踪、质谱和数学分析方法，以确定循环营养素的直接来源、它们的相互转化率，以及最终对TCA循环代谢的组织特异性贡献。使用15种营养素示踪剂进行的实验能够广泛解释高碳水化合物或生酮饮食喂养和禁食小鼠的循环代谢周期和组织TCA输入。我们发现，大部分循环碳通量由两个主要循环进行：葡萄糖乳酸和甘油三酯甘油脂肪酸。当相关营养素的饮食含量较低时，通过这些途径的徒劳循环是显著的，这使得内部代谢活动对食物选择具有鲁棒性。所提出的活体流量量化方法广泛适用于不同的生理和疾病状态。

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  • 来源
    《Cell metabolism》 |2020年第4期|共17页
  • 作者

    Hui Sheng; Cowan Alexis J.; Zeng Xianfeng; Yang Lifeng; TeSlaa Tara; Li Xiaoxuan; Bartman Caroline; Zhang Zhaoyue; Jang Cholsoon; Wang Lin; Lu Wenyun; Rojas Jennifer; Baur Joseph; Rabinowitz Joshua D.;

  • 作者单位

    Princeton Univ Lewis Sigler Inst Integrat Genom Washington Rd Princeton NJ 08544 USA;

    Princeton Univ Lewis Sigler Inst Integrat Genom Washington Rd Princeton NJ 08544 USA;

    Princeton Univ Lewis Sigler Inst Integrat Genom Washington Rd Princeton NJ 08544 USA;

    Princeton Univ Lewis Sigler Inst Integrat Genom Washington Rd Princeton NJ 08544 USA;

    Princeton Univ Lewis Sigler Inst Integrat Genom Washington Rd Princeton NJ 08544 USA;

    Princeton Univ Lewis Sigler Inst Integrat Genom Washington Rd Princeton NJ 08544 USA;

    Princeton Univ Lewis Sigler Inst Integrat Genom Washington Rd Princeton NJ 08544 USA;

    Princeton Univ Lewis Sigler Inst Integrat Genom Washington Rd Princeton NJ 08544 USA;

    Princeton Univ Lewis Sigler Inst Integrat Genom Washington Rd Princeton NJ 08544 USA;

    Princeton Univ Lewis Sigler Inst Integrat Genom Washington Rd Princeton NJ 08544 USA;

    Princeton Univ Lewis Sigler Inst Integrat Genom Washington Rd Princeton NJ 08544 USA;

    Univ Penn Perelman Sch Med Dept Physiol 3400 Civ Blvd Philadelphia PA 19104 USA;

    Univ Penn Perelman Sch Med Dept Physiol 3400 Civ Blvd Philadelphia PA 19104 USA;

    Princeton Univ Lewis Sigler Inst Integrat Genom Washington Rd Princeton NJ 08544 USA;

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  • 正文语种 eng
  • 中图分类 内分泌腺疾病及代谢病;
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